Pathogenesis of HIV-associated chronic lung disease among vertically-infected children and adolescents

Investigator: John Metcalfe, MD

Location(s): Zimbabwe

Parent Project: UCSF-Gladstone Center for AIDS Research (CFAR)


HIV continues to impose a heavy burden on pediatric care services in sub-Saharan Africa, where 90% of the estimated 630,000 HIV-infected children receiving antiretroviral therapy (ART) live. The availability of ART has resulted in increasing numbers of HIV-infected infants surviving to older childhood, and respiratory conditions are the leading cause of death in this group. Recently, a novel form of chronic lung disease (CLD) has been described that may affect up to one-third of children aged 10 years and older in HIV care in Southern Africa. An intriguing possibility underlying the development of this unique condition relates to HIV-associated chronic inflammation during a period of rapid development of the immune system and, by extension, the composition and diversity of lower airway and gastrointestinal bacterial communities. This possibility will be explored by a multi-disciplinary collaborative team of physician-scientists, immunologists, microbiologists, including experts on the microbiome, bioinformatics, and epidemiology. We are currently undertaking a prospective cohort study within a large pediatric HIV clinic in Harare, Zimbabwe to characterize in detail the prevalence, clinical manifestations of, and risk factors for CLD among HIV-infected children. In the current proposal, we seek a CFAR Mentored Scientist Award to support an integrated aim analyzing microbial composition of biologic specimens (Lynch lab, UCSF) collected and cryopreserved during Year 1. We anticipate that this CFAR proposal will give crucial preliminary insights to potentially modifiable immune targets as well as identify strong bacterial candidates for therapeutic intervention.